Lactate and lactylation in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 11, 2025

Abstract Accumulated evidence has implicated the diverse and substantial influence of lactate on cellular differentiation fate regulation in physiological pathological settings, particularly intricate conditions such as cancer. Specifically, been demonstrated to be pivotal molding tumor microenvironment (TME) through its effects different cell populations. Within cells, impacts signaling pathways, augments shuttle process, boosts resistance oxidative stress, contributes lactylation. In various populations, interplay between immune cells governs processes differentiation, response, surveillance, treatment effectiveness. Furthermore, communication stromal/endothelial supports basal membrane (BM) remodeling, epithelial-mesenchymal transitions (EMT), metabolic reprogramming, angiogenesis, drug resistance. Focusing production transport, specifically dehydrogenase (LDH) monocarboxylate transporters (MCT), shown promise Inhibitors targeting LDH MCT act both suppressors enhancers immunotherapy, leading a synergistic therapeutic effect when combined with immunotherapy. The review underscores importance progression provides valuable perspectives potential approaches that target vulnerability metabolism, highlighting Heel Achilles for cancer treatment.

Language: Английский

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Self‐Sustained Biophotocatalytic Nano‐Organelle Reactors with Programmable DNA Switches for Combating Tumor Metastasis

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Metastasis, the leading cause of mortality in cancer patients, presents challenges for conventional photodynamic therapy (PDT) due to its reliance on localized light and oxygen application tumors. To overcome these limitations, a self‐sustained organelle‐mimicking nanoreactor is developed here with programmable DNA switches that enables bio‐chem‐photocatalytic cascade‐driven starvation‐photodynamic synergistic against tumor metastasis. Emulating compartmentalization positional assembly strategies found living cells, this nano‐organelle reactor allows quantitative co‐compartmentalization multiple functional modules designed self‐illuminating chemiexcited PDT system. Within space‐confined nanoreactor, biofuel glucose converted hydrogen peroxide (H 2 O ) which enhances luminol‐based chemiluminescence (CL), consequently driving generation photochemical singlet ( 1 via resonance energy transfer. Meanwhile, hemoglobin functions as synchronized supplier both oxidation PDT, while also exhibiting peroxidase‐like activity produce hydroxyl radicals (·OH). Crucially, keeps switching off normal tissues, on‐demand activation tumors through toehold‐mediated strand displacement. These findings demonstrate self‐sufficient precise striking tumors, promising paradigm managing highly metastatic cancers.

Language: Английский

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Mitochondrial Sirtuins in Cancer: A Revisited Review from Molecular Mechanisms to Therapeutic Strategies

Theranostics, Journal Year: 2024, Volume and Issue: 14(7), P. 2993 - 3013

Published: Jan. 1, 2024

The sirtuin (SIRT) family is well-known as a group of deacetylase enzymes that rely on nicotinamide adenine dinucleotide (NAD

Language: Английский

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Lactoferrin-Encapsulated Dichloroacetophenone (DAP) nanoparticles enhance drug delivery and anti-tumor efficacy in prostate cancer

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217522 - 217522

Published: Feb. 1, 2025

Language: Английский

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Targeting PI3K signaling in Lung Cancer: advances, challenges and therapeutic opportunities

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 14, 2025

Abstract Lung cancer remains the leading cause of cancer-related mortality globally, necessitating continual exploration novel therapeutic targets. The phosphoinositide 3-kinase (PI3K) signaling pathway plays a pivotal role in oncogenic processes, including cell growth, survival, metabolism and immune modulation. This comprehensive review delineates distinct roles PI3K subtypes—PI3Kα, PI3Kβ, PI3Kγ PI3Kδ—in lung pathogenesis progression. We evaluate current landscape inhibitors, transitioning from non-selective early-generation compounds to isoform-specific agents, highlighting their clinical efficacy, resistance mechanisms potential combination strategies. Furthermore, intricate interplay between tumor microenvironment is explored, elucidating how modulation can enhance immunotherapeutic responses. Metabolic reprogramming driven by also dissected, revealing vulnerabilities that be therapeutically exploited. Despite promising advancements, challenges such as adverse effects underscore need for personalized medicine approaches development next-generation inhibitors. underscores multifaceted advocates integrated strategies harness its full potential, paving way improved patient outcomes.

Language: Английский

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Integration of scRNA-seq and bulk RNA-seq to reveal the association and potential molecular mechanisms of metabolic reprogramming regulated by lactylation and chemotherapy resistance in ovarian cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Objective Ovarian cancer (OC) ranks among the foremost causes of mortality in gynecological malignancies, with chemoresistance being primary factor contributing to unfavorable prognosis. This work seeks clarify mechanisms resistance-related lactylation OC, intending offer novel theoretical foundations and therapy strategies for addressing chemoresistance. Methods Through combined analysis bulk RNA-seq single-cell data, we initially found genes linked Subsequently, employed differential expression analysis, survival enrichment other methodologies further investigate roles molecular these tumor resistance. Ultimately, investigated resistant non-resistant tissues cells via experimentation. Results We two candidate associated chemoresistance, ALDH1A1 S100A4. Analysis data indicated that represent cell subpopulation relevant resistance studies. Subpopulation several subtypes were markedly resistance, elevated levels S100A4 subpopulation, notably correlating various immunological metabolic pathways. pathways oxidative phosphorylation glycolysis activity was lactic acid buildup The investigation marker gene protein-protein interaction network subgroup elucidated intricate interactions genes. OC platinum-resistant cohort compared sensitive cohort, a considerable rise observed cells, demonstrating co-localization lactylation. Conclusion elucidates significant function identifies as possible drug These findings enhance our comprehension behind critical insights formulation therapeutic options.

Language: Английский

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Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 8, 2025

Epigenomic modifications—such as DNA methylation, histone acetylation, and methylation—and their implications in tumorigenesis, progression, treatment have emerged a pivotal field cancer research. Tumors undergo metabolic reprogramming to sustain proliferation metastasis nutrient-deficient conditions, while suppressing anti-tumor immunity the tumor microenvironment (TME). Concurrently, immune cells within immunosuppressive TME adaptations, leading alterations function. The complicated interplay between metabolites epigenomic modulation has spotlighted significance of regulation immunometabolism. In this review, characteristics modification associated with tumors are systematically summarized alongside regulatory roles Classical emerging approaches delineated broaden boundaries research on crosstalk immunometabolism epigenomics. Furthermore, we discuss potential therapeutic strategies that target modulate modifications, highlighting burgeoning synergy therapies immunotherapy promising avenue for treatment.

Language: Английский

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Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2846 - 2846

Published: Feb. 29, 2024

The treatment of patients with advanced cancer poses clinical problems due to the complications that arise as disease progresses. Bone metastases are a common problem may face, and currently, there no effective drugs treat these individuals. Prostate, breast, lung cancers often spread bone, causing significant disabling health conditions. bone is highly active dynamic tissue considered favorable environment for growth cancer. role osteoblasts osteoclasts in process remodeling way which their interactions change during progression metastasis critical understanding pathophysiology this disease. These create self-perpetuating loop stimulates metastatic cells bone. metabolic reprogramming both microenvironment has serious implications development metastasis. Insight into systemic elements regulate process, well cellular changes occur metastases, discovery cure It crucial explore different therapeutic options focus specifically on malignancy order effectively This review will effects disorders factors like hormones cytokines metastases. We also examine various alternatives available today upcoming advances novel treatments.

Language: Английский

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Deciphering the oncogenic network: how C1QTNF1-AS1 modulates osteosarcoma through miR-34a-5p and glycolytic pathways

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 9, 2025

Osteosarcoma (OS), a prevalent metastatic cancer among young individuals, is associated with grim prognosis. Long non-coding RNAs (lncRNAs), including C1QTNF1-AS1, are pivotal regulators of cell proliferation and motility. As an oncogene, C1QTNF1-AS1 implicated in various tumor types, such as colorectal, pancreatic, hepatocellular carcinomas, OS. The aim this study was to investigate the functions underlying mechanisms progression osteosarcoma. This investigation focused on elucidating functional roles OS cells. Bioinformatics tools were utilized identify interaction between microRNA miR-34a-5p well targeting LDHA PDK3 by miR-34a-5p. Dual-luciferase reporter assays RNA immunoprecipitation employed validate these interactions. Expression profiles miR-34a-5p, LDHA, osteosarcoma cells analyzed using RT-PCR western blot analyses, revealing their intricate relationships. impact molecules proliferation, invasion, migration assessed through CCK-8, Transwell, Cell scratch assay. Moreover, effects aerobic glycolysis examined quantifying ATP levels, lactate production, glucose uptake capacity, extracellular acidification rate. findings indicated significant decrease expression levels compared normal osteoblasts. A parallel downregulation trend also observed Silencing led marked upregulation cells, which partially attenuated mimics. Functional evaluations demonstrated that suppression accelerated growth, motility, invasiveness, Warburg effect. Conversely, overexpression mitigated stimulatory effects, suggesting regulatory role modulating progression. Our research emphasizes critical pathogenesis (OS). We discovered indirectly upregulates suppressing regulator cascade events promotes enhancing glycolytic metabolism supplying energy for migration, invasion. These suggest potential therapeutic target highlight importance understanding network involving lncRNAs

Language: Английский

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Repurposing Brucine as a Chemopreventive Agent in Mammary Gland Carcinoma: Regulating Lactate Transport through MCT-4

Toxicology Reports, Journal Year: 2025, Volume and Issue: 14, P. 101902 - 101902

Published: Jan. 10, 2025

Language: Английский

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